Keywords: breast cancer, cancer stem cells, novel therapies, tumor microenvironment.IntroductionBreast cancer is the globally most common malig-nancy amongst women. The incidence hasincreased dramatically over the last decades, par-ticularly in the developing world. In 1980, 600 000women were diagnosed with breast cancer,whereas 1.6 million received the same diagnosisin 2010 [1]. On the basis of these figures, it isobvious that preventive measurements are needed,combined with novel therapy strategies based ontumour biological characteristics.The mortality from breast cancer has decreased byaround 30–40% since 1980s due to the use ofadjuvant therapies and early detection. Targetedtherapies such as trastuzumab (a monoclonal anti-bodythatblocksHER2/neureceptorfunctions)andother anti-HER2-based drugs like lapatinib, pert-uzumabandTDM-1havelatelybeeninfocus.Thesedrugs, in particular if used in combination togetherwith chemotherapy, improve outcome in the meta-static setting. There is hope that improved use ofthese and other similar drugs may ultimately resultin cure. The curative potential has already beendemonstrated in the adjuvant and neoadjuvantsettings. In the latter, histopathological remissionisobtainedinmorethan50%ofthecaseswhenusedin combination with chemotherapy.At the June 2012 Nobel conference ‘Breast cancer;progress and challenges in prevention, risk predic-tion, tumour biology and treatment’, world-leadingexperts gathered to discuss recent findings relatedto breast cancer biology and treatment. In additionto major support from the Nobel Assembly atKarolinska Institutet, the meeting was also spon-sored by the Swedish Research Council, the Swed-ish Cancer Society, Journal of Internal Medicine(JIM) and the Karolinska Institutet-funded BRECTbreast cancer research network.Some of the major and important topics arediscussed in five review papers of this JIM issue.In this introductory paper, we address and intro-duce each of them.Host and tumour cell interactionsIt is increasingly recognized that the tumourmicroenvironment exerts important regulatoryfunctions that influence tumour growth andmetastasis. Two reviews in this JIM issue addressthe complex roles of hypoxia and the importance ofactivation of stromal cells at metastatic sites [2, 3].The review by Rundqvist and Johnson describeshow hypoxia induces functional alterations invarious cells of the tumour microenvironment,including macrophages, vascular cells and fibro-blasts [2]. These responses affect metastasisthrough multiple mechanisms, including altera-tions in the paracrine signalling to malignant cellsand changes in the functional characteristics of thevasculature or immune cells.The classical ‘seed-and-soil’ hypothesis of cancermetastasis emphasizes the importance of host cell–tumour cell interactions in metastasis. These ideasreceive new support through a series of findingsoutlining the importance of host cell activation inmetastatic seeding [3]. A number of recent exper-imental studies suggest that the activation of such‘pre-metastatic niches’ includes both recruitmentof bone marrow–derived cells and activation ofresident cells including fibroblast. Obviously, tar-geting of these processes is a highly interestingstrategy for adjuvant cancer therapy.Mammary stem cells and tumour initiating cellsImportant progress in the characterization of nor-mal tissue stem cells, and their progenitors, hasbeen made over the recent past. This is relevantbecause the phenotype of breast cancer cells isinfluenced both by the tumour cell of origin and thepresence of specific somatic genetic alterations,including activation of oncogenes or inactivation of